Pre-patterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B
Transcriptomics Dataset
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| Accession | GSE63346 |
| Title | Pre-patterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B |
| Description | Dynamic interactions of nuclear lamins with chromatin through so-called lamin-associated domains (LADs) contribute to spatial arrangements of the genome. Here, we provide evidence for pre-patterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified by the nutrient sensor O-linked N-acetylglucosamine (H2BGlcNAc), which we term GADs. We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving (i) a spreading of lamin A/C-chromatin interactions during the transition from progenitor cell proliferation to cell cycle arrest, and (ii) a genome-scale redistribution these interactions through a process of LAD exchange within hours of adipogenic induction. Chromatin state modeling reveals that lamin A/C LADs can be found both in active and repressive chromatin contexts which can be influenced by cell differentiation status. De novo formation of adipogenic lamin A/C LADs occurs non-randomly on GADs, consisting of megabase-size intergenic and repressive chromatin domains. Accordingly, while pre-differentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. Moreover, release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional upregulation after adipogenic induction, and with concordant downstream elevations in H2BGlcNAc levels and O-GlcNAc cycling. Our results unveil an epigenetic pre-patterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63346 |
| Repository | Gene Expression Omnibus |
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